Identification of DEGs and transcription factors involved in H. pylori-associated inflammation and their relevance with gastric cancer

Abstract

Background Previous studies have indicated that chronic inflammation linked to H. pylori infection is the leading causes for gastric cancer (GC). However, the exact mechanism is not entirely clear until now. Purpose To identify the key molecules and TFs involved in H. pylori infection and to provide new insights into H. pylori-associated carcinogenesis and lay the groundwork for the prevention of GC. Results GO and KEGG analysis revealed that the DEGs of Hp+-NAG were mainly associated with the immune response, chemokine activity, extracellular region and rheumatoid arthritis pathway. The DEGs of Hp+-AG-IM were related to the apical plasma membrane, intestinal cholesterol absorption, transporter activity and fat digestion and absorption pathway. In Hp+-NAG network, the expression of TNF, CXCL8, MMP9, CXCL9, CXCL1, CCL20, CTLA4, CXCL2, C3, SAA1 and FOXP3, JUN had statistical significance between normal and cancer in TCGA database. In Hp+-AG-IM network the expression of APOA4, GCG, CYP3A4, XPNPEP2 and FOXP3, JUN were statistically different in the comparison of normal and cancer in TCGA database. FOXP3 were negatively associated with overall survival, and the association for JUN was positive. Conclusion The current study identified key DEGs and their transcriptional regulatory networks involved in H. pylori-associated NAG, AG-IM and GC and found that patients with higher expressed FOXP3 or lower expressed JUN had shorter overall survival time. Our study provided new directions for inflammation-associated oncogenic transformation involved in H. pylori infection.

[Retracted] Clinical Effect of Clarithromycin Combined with Tinidazole on Helicobacter pylori‐Related Gastritis and Its Influence on COX‐2 Expression

“…BioMed Research International this is the uncharacterized Helicobacter pylori protein HP1173 whose secretion levels vary significantly among strains. Recombinant HP1173 (rHP1173) was able to bind to THP-1 monocyte-derived macrophages, resulting in the production of the proinflammatory cytokines, tumor necrosis factor (TNF), and IL-1β, as well as the C-X-C motif chemokine ligand 8 (CXCL8), in a dose-and time-dependent manner [19].…”

“…With the passage of time, gastric mucosa will undergo further loss of glandular cells, which will eventually deteriorate into atrophic gastritis. Helicobacter pylori does not usually interact directly with immune cells in the stomach, yet components of the bacterium can exert their effects on these cells, leading to modulation of host inflammation [ 6 , 12 , 19 ]. Indeed, studies in an Helicobacter pylori mouse infection model showed that Helicobacter pylori vacuolating cytotoxin A (VacA) targets gastric lamina propria myeloid cells, thereby suppressing interleukin-23 (IL-23) expression by dendritic cells and inducing IL-10 and transforming growth factor- β (TGF- β ) expression in macrophages.…”

“…Indeed, studies in an Helicobacter pylori mouse infection model showed that Helicobacter pylori vacuolating cytotoxin A (VacA) targets gastric lamina propria myeloid cells, thereby suppressing interleukin-23 (IL-23) expression by dendritic cells and inducing IL-10 and transforming growth factor- β (TGF- β ) expression in macrophages. It was suggested that Helicobacter pylori uses VacA to promote tolerogenesis in the host [ 19 ]. Helicobacter pylori bacterial factors can also upregulate proinflammatory responses in immune cells thus leading to an exacerbation of inflammation.…”

Multi-omics reveals microbiome, host gene expression, and immune landscape in gastric carcinogenesis

“…Differential gene expression analysis of gastric cancer tissue showed that several cancer-related biological pathways, including ‘Mitogen-Activated Protein Kinase signaling’ and ‘Cell cycle’, were associated with gastric cancer ( Shi et al., 2021 ). Moreover, HP-associated non-atrophic gastritis was found to be associated with the upregulation of genes related to ‘Immune response’ and ‘Chemokine activity’ pathways ( Yin et al., 2020 ). These pathways are related to chronic gastric inflammation, which may induce precancerous changes in the gastric mucosa (atrophic gastritis and intestinal metaplasia).…”

HDAC6/FOXP3/HNF4α axis promotes bile acids induced gastric intestinal metaplasia

“…However, no consensus has been reaching regarding the role of FOXP3 in GC. Some studies have shown that FOXP3 can promote tumor occurrence in gastric cells, while other studies have revealed that it may inhibit the progression of GC [36,37]. Furthermore, the role of FOXP3 in IM has not yet been reported.…”